Title: Interstrand DNA Cross-Links Derived from Reaction of a 2-Aminopurine Residue with an Abasic Site.
Authors: Nejad, Maryam Imani; Price, Nathan E; Haldar, Tuhin; Lewis, Calvin; Wang, Yinsheng; Gates, Kent S
Published In ACS Chem Biol, (2019 07 19)
Abstract: Efficient methods for the site-specific installation of structurally defined interstrand cross-links in duplex DNA may be useful in a wide variety of fields. The work described here developed a high-yield synthesis of chemically stable interstrand cross-links resulting from a reductive amination reaction between an abasic site and the noncanonical nucleobase 2-aminopurine in duplex DNA. Results from footprinting, liquid chromatography-mass spectrometry, and stability studies support the formation of an N2-alkylamine attachment between the 2-aminopurine residue and the Ap site. The reaction performs best when the 2-aminopurine residue on the opposing strand is offset 1 nt to the 5'-side of the abasic site. The cross-link confers substantial resistance to thermal denaturation (melting). The cross-linking reaction is fast (complete in 4 h), employs only commercially available reagents, and can be used to generate cross-linked duplexes in sufficient quantities for biophysical, structural, and DNA repair studies.
PubMed ID: 31259519
MeSH Terms: 2-Aminopurine/chemistry*; Amination; Cross-Linking Reagents/chemistry*; DNA/chemistry*; Models, Molecular; Nucleic Acid Conformation; Nucleic Acid Denaturation; Oxidation-Reduction